ArticleNature cell biology2015
ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation.
Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 414 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
414 citing papers in PubMed, 2 syntheses or guidelines pooled it, 667 citations in OpenAlex.
- Genomic data-driven framework for drug target discovery in atrial fibrillation.Journal of translational medicine · 2025Pooled it
- A meta-analysis and systematic review of myocardial infarction-induced cardiomyocyte proliferation in adult mouse heart.BMC medicine · 2024Pooled it
- Click chemistry-modified cardiomyocytes enhance cardiac contractility and prevent remodeling in ischemia-reperfusion injured hearts.Bioactive materials · 2027Article
- Maternal Exercise and Offspring Cardiac Regenerative Potential: Roles of Apelin and α-Ketoglutarate.Biology · 2026Review
- Small-molecule cocktail 2SM promotes heart regeneration via inducing embryonic-like cardiomyocyte state.Cell regeneration (London, England) · 2026Article
- Mechanical unloading promotes adult cardiomyocyte proliferation through epicardial NRG1-ERBB4 signaling.Nature cardiovascular research · 2026Article
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Titin cleavage in living cardiomyocytes induces sarcomere disassembly but does not trigger cell proliferation.The Journal of biological chemistry · 2026Article
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Retinol saturase in the mitochondria antagonizes IDH2 and GLUD1 acetylation to mediate heart repair.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Epithelial-to-mesenchymal transition as a central driver of tumor cell plasticity.Nature cancer · 2026Review
- Cell-cycle regulation of sarcomere integrity-Role for Actn2 phosphorylation.Physiological reports · 2026Article
- Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026Review
- Transcriptional regulation in heart development, disease and regeneration: reassessing the fetal gene hypothesis.Nature reviews. Cardiology · 2026Review
- Avenues for optimization of cardiac therapeutics by minimally invasive delivery.Acta biomaterialia · 2026Review
- Exploring the Potential Mechanism of Polyethylene Terephthalate Associated Cardiotoxicity through Network Toxicology and Molecular Docking.ACS omega · 2026Article
- Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026Review
- Harnessing glucocorticoid receptor antagonism to enhance the efficacy of cardiac regenerative growth factors and cytokines.Nature cardiovascular research · 2026Article
354 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages. Induction of a constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs resulted in cardiomegaly, characterized by extensive CM hypertrophy, dedifferentiation and proliferation, differentially mediated by ERK, AKT and GSK3β/β-catenin signalling pathways. Transient induction of caERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.